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Preterm Birth

Although WHO has defined the upper limit of prematurity as a gestational age of 36 weeks and 6 days, the lower limit is determined by fetal organ development and advances in high-risk obstetric and neonatal intensive care. Dramatic decreases in neonatal mortality rates and gestational age-specific neonatal mortality rates have been associated with a concomitant lowering of the limit of viability (Alexander et al., 1999 Allen et al., 2000, Appendix B). A current concern is that a biological...

A variety of agricultural chemicals are manufactured and widely applied in the United States and worldwide to control pests and enhance agricultural productivity. Human exposures may result from occupational manufacture or use or may be indirect as a result of contamination of environmental media, such as water, air, and food. Among the agricultural chemicals, pesticides have been the most intensively studied for their association with preterm birth. Some of the most notorious pesticides, such...

To operationalize the current definition of prematurity, accurate measures of the duration of pregnancy (i.e., gestational age) are needed. Several methods are used to determine gestational age, but many are based on prenatal ultrasounds, which have provided a window onto the fetus and allowed observation of fetal growth and development (Goldstein et al., 1988 Neilson, 2000 Nyberg et al., 2004 Timor-Tritsch et al., 1988 Warren et al., 1989). Most often, prenatal ultrasounds determine pregnancy...

In 2004, 12.5 percent of births in the United States were preterm that is, born at less than 37 completed weeks of gestation. This rate has increased steadily in the past decade. There are significant, persistent, and very troubling racial, ethnic, and socioeconomic disparities in the rates of preterm birth. The highest rates are for non-Hispanic African Americans, and the lowest are for Asians or Pacific Islanders. In 2003, the rate for African-American women was 17.8 percent, whereas the...

A significant and relatively recent effort has been made to link environmental air pollution exposures with preterm birth. Recent reviews examined a subset of articles on this topic in detail and drew different conclusions (Maisonet et al., 2004 Sram et al., 2005). Sram et al. (2005) reported that the evidence was insufficient to derive conclusions about an association between air pollution exposure and preterm birth and that further studies were justified. In contrast, Maisonet et al. (2004)...

High levels of alcohol use during pregnancy have obvious adverse effects on fetal development (AAP, 1993 Spohr et al., 1993). There is consistent support of an adverse effect for heavier users of alcohol for example, women who have more than one drink per day, on average, have an increased risk of preterm birth (Albertsen et al., 2003 Kesmodel et al., 2000 Lar-roque, 1992 Lundsberg et al., 1997 Parazzini et al., 2003). Subject to the question of the accuracy of self-reported information on...

One possible reason for a genetic influence on racial disparities in preterm birth is that susceptibility variants may be present in one population but absent in others or may vary in frequencies across diverse populations. This may affect the number of individuals at increased risk for preterm birth. One obvious example is the unequal distribution of disease-associated alleles for certain recessive disorders, such as sickle cell disease or Tay-Sacks disease. One study examined a total of 179...

Although most animal species do not have significant rates of spontaneous preterm birth, there is much interest in the use of relevant animal models to elucidate the mechanisms of preterm birth and the neonatal sequelae of prematurity and to develop rationale and efficacious treatment and prevention strategies. However, in choosing an appropriate animal model, a necessary caveat is that many species differ from humans in the length of gestation and the number of fetuses, the type of...

Spontaneous preterm birth occurs infrequently in most species. This has limited research in this area to specific pharmacological or environmental interventions that result in preterm birth. Pharmacological administration of RU-486, a progesterone antagonist, leads to preterm delivery in rodents but not in nonhuman primates (Dudley et al., 1996 Garfield et al., 1987 Ha-luska et al., 1994). Administration of cortisol (Grigsby et al., 2000) or maternal starvation (protein and caloric restriction)...

Three themes repeatedly emerged at the start of the committee's deliberations that helped to organize the committee's thinking and approach to this problem. The first was a need for clarity of terminology. In the literature, terms characterizing the duration of gestation, fetal growth, and maturation have been applied inconsistently and have been used interchangeably. This has made it difficult to interpret the data on the causes and consequences of preterm birth and to evaluate treatments. The...

The ear begins to develop at the end of 6 weeks of gestation and is fully developed by 20 weeks if gestation. A response to sound can be demonstrated in fetuses and infants born at 23 and 24 weeks of gestation, and auditory brainstem-evoked responses can be recorded this early in preterm infants (Allen and Capute, 1986 Birnholz and Benacerraf, 1983 Starr et al., 1977). The shape of the waveform changes and the conduction time decreases with increasing gesta-tional or postmenstrual age. One to...

A special interest in behavioral influences on preterm birth is well justified, given that these are subject to change and could reduce the frequency of preterm birth directly. As previously reviewed in some detail (Berkowitz and Papiernik, 1993 Savitz and Pastore, 1999), a large number of observational studies of a range of health behaviors, including tobacco and alcohol use, nutrition, and physical activity, have been conducted. Although each of these behaviors poses specific challenges in...

The detection of uterine contractions through maternal self-perception (Mercer et al., 1996) and electronic monitoring (Iams et al., 2002 Main et al., 1993 Nageotte et al., 1988) has been studied to predict preterm delivery. The threshold number of contractions most often studied is four per hour. An increased frequency of self-reported contractions is associated with preterm delivery before 35 weeks of gestation in both nulliparous women (RR 2.41 95 percent confidence interval CI 1.47 to 3.94...

The significance of the racial and ethnic differences of human populations is frequently debated in clinical, epidemiological, and molecular research (Ioannidis et al., 2004). The undeniable evidence of health disparities between individuals of different races and ethnicities indicates that in some cases a correlation exists between race and health or disease. However, this relationship is complex and poorly understood. First, it is essential to point out that there are no generally agreed upon...

The Centers for Disease Control and Prevention (CDC) defines ARTs as procedures in which the egg and the sperm are handled in the laboratory, including in vitro fertilization (IVF) as well as related procedures, such as intracytoplasmic sperm injection (ICSI) and gamete intrafallopian transfer (GIFT) or zygote intrafallopian transfer (ZIFT) (Table 5-2). Since 1996, the federal government has mandated that all clinics performing procedures involving ARTs report their outcomes to the CDC (Meis et...

Preterm infants can experience a variety of cardiovascular disorders, ranging from major morphological defects to dysfunctional autoregulation of blood vessels (hypotension). By embryonic day 20, the cells that will form the heart begin to differentiate (Maschoff and Baldwin, 2005 Schultheiss et al., 1995). The primitive heart beats by 4 weeks of gestation and is fully formed at the end of the 6th week. Because gas exchange occurs in the placenta, most of the fetal blood flow bypasses the lungs...

Outside of the initial hospitalization, there has been a paucity of research on the out-of-pocket travel costs for caregivers associated with the incremental medical services provided to preterm infants. Productivity losses have also received scant attention (Zupancic, 2006), although such caregiver costs for disabling conditions can exceed the costs of care for the affected individuals themselves (Tilford et al., 2001). One recent study among large employers, in which mothers were both...

Research progress on preterm birth and infants born preterm will require scientists from many disciplines working in concert. Physician scientists from obstetrics and gynecology are an important component of such teams. What is needed is a paradigm shift in the field of obstetrics and gynecology to provide clinical investigators who can translate the research findings that come from basic science laboratories or pharmaceutical companies into new clinical diagnostic and treatment knowledge. The...

Because of the widespread use of chlorination as a means to disinfect drinking water supplies, there is considerable interest in the potential health risks from the by-products that are formed because of chlorination disinfection. The principal by-products are trihalomethanes (e.g., chloroform, bromodichloromethane, and dichlorobromomethane), haloacetic acids (e.g., trichloroacetic acid and dichloroacetic acid), and Studies of the health effects of chlorination disinfection by-products are...

A second set of studies involved a common chronic stressor, such as being imprisoned (Hollander, 2005) or homeless (Stein et al., 2000) during pregnancy or experiencing a catastrophic event occurring during pregnancy (Glynn et al., 2001 Lederman et al., 2004). For example, Lederman and colleagues (2004) assessed the impact of the time of gestation at the time of the World Trade Center terrorist attack on September 11, 2001, among 300 nonsmoking women in New York City who were pregnant at the...

In general, the risks for preterm birth have been individualized that is, those characteristics of individuals that increase the likelihood of preterm delivery within groups rather than the environmental and social factors that affect the rates of preterm birth among the population as a whole (Goldenberg et al., 1998) are emphasized. However, as discussed in Chapter 3 and the previous section on sociodemographic factors, observational studies do not consistently demonstrate strong associations...

For many years, attention has focused on high-risk obstetric and neonatal intensive care for extremely preterm infants and infants born at the lower limit of viability, although very little attention has been paid to the majority of preterm infants who are born near term (also called late-preterm infants). Although many deliveries of near-term infants are spontaneous or are indicated for maternal or fetal circumstances, it is important to keep in mind that these larger preterm infants born near...

Developmental immaturity affects a wide range of organ systems. This section describes the short-term complications of preterm birth in terms of fetal development as well as injury to fragile organ systems during the perinatal and neonatal periods. Many of these complications have lifelong consequences for the health, growth, and development of infants born preterm. As described in Chapter 6, the complex interplay of the mechanisms involved in preterm delivery, including inflammation and...

The overall high rate of preterm birth in the United States and the persistent racial-ethnic gap is one of the most significant public health problems today. Despite many years of observational and clinical research, the exposures that place women at risk are not well understood. The substantial intergroup as well as intragroup variabilities in the risk of preterm birth have been shown to be related related to socioeconomic condition, nativity, acculturation, or other maternal characteristics....

The cost of preterm birth to the nation exceeds 26.2 billion annually and 51,500 per infant born preterm. Although a disproportionate share of these costs are incurred in the form of neonatal intensive medical care services and among those born extremely preterm, the estimates provided in this chapter demonstrate that substantial incremental costs associated with preterm birth extend after the initial hospitalization and among the majority of infants born even just a few weeks preterm....

Improve the Methods of Identifying and Treating Women at Risk for Preterm Labor In the past 30 years, important strides in obstetric and neonatal tertiary care have been made to reduce the rates of infant morbidity and mortality as a result of preterm birth. However, the primary and secondary interventions implemented to date have not reduced the rate of pre-term birth. Current prenatal care is focused on risks other than preterm birth. Birth defects, adequate fetal growth, preeclampsia,...

The societal costs associated with illness are conventionally broken down into direct and indirect costs. Direct costs include the value of the resources used to treat the condition, such as medical care, special education, and developmental services. Indirect costs include the value of resources lost to society, such as the reduced labor market productivity or the reduced level of household productivity due to heightened morbidity or premature mortality. Costs are incremental relative to...

Lion in 2005, or 51,600 per infant born preterm. The share that medical care services contributed to the total cost was 16.9 billion ( 33,200 per preterm infant), or about two-thirds of the total cost, with more than 85 percent of that medical care delivered during infancy. Maternal delivery costs contributed another 1.9 billion ( 3,800 per preterm infant). Special education services associated with a higher prevalence of four disabling conditions (cerebral palsy, mental retardation, hearing...

The World Health Organization (WHO) has defined preterm birth as delivery before 37 completed weeks of gestation. By convention, gestational age is reported in terms of completed weeks (i.e., one never rounds gestational age up, so 36 weeks and 6 days of gestation is 36 weeks and not 37 weeks of gestation). This definition makes the distinction between being born early and being born too small. Determining when natural conception takes place is difficult (see below), so birth weight (not...

As discussed in Chapter 4, socioeconomic differences in multiple gestations have not been well studied (Kramer et al., 2000). The literature on infertility, utilization of treatment, and outcomes of treatment has been focused on white and socieconomically advantaged populations. While the extent to which various racial-ethnic minority populations and subpopulations experience fertility problems is not precisely known , a series of recent reports developed from a workshop, Health Disparities in...

A number of indirect lines of evidence suggest that the practice of vaginal douching might increase the risk of preterm birth. Douching is a common behavior and is more common among African-American women than white women, consistent with the increased prevalence of bacterial vaginosis (BV) and preterm birth among African-American women (Bruce et al., 2000). Furthermore, douching alters the vaginal microflora and may well facilitate the passage of vaginal pathogens to the upper reproductive...

Economic evaluation of interventions that can be used to reduce the rates of preterm birth and its adverse consequences can aid in decision making regarding the development and integration of new technologies and programs. The techniques for such an evaluation take on several different forms. Cost identification assesses the burden of illness and the features of its distribution in economic terms, as with the estimates provided above. Such estimates can form part of the foundation for the...

Through the Individuals with Disabilities Education Act (IDEA which was renewed in 2004) (DOE, 2005), children with long-term health conditions receive a variety of services. The original legislation underlying these programs called for assuring the free appropriate public education in the least restrictive environment. The two main IDEA programs include early in tervention services and special education. Early intervention services cover children from birth to 3 years of age, at which point...

The available literature has provided some evidence of familial and intergenerational influences on low birth weight or preterm birth (Bakketeig et al., 1979 Carr-Hill and Hall, 1985 Khoury and Cohen, 1987 Porter et al., 1997 Varner and Esplin, 2005). A population-based cohort study of data from birth certificates and fetal death certificates from the state of Georgia between 1980 and 1995 suggest that the recurrence of preterm delivery contributes to a notable portion of all preterm births,...

A variety of approaches have been used to estimate exposures and to investigate the associations between environmental chemical exposures and preterm birth. A common approach has been to use employment or location of residence as a proxy for exposure, such as working with pesticides, proximity to a pollution source, or residence in a polluted locality. In those studies, exposure is typically estimated from measurement of the levels of contamination of common environmental media, such as...

Several studies have estimated the excess maternal costs associated with the birth of an LBW infant and with preterm birth (Zupancic, 2006). Most such studies focused strictly on elevated delivery costs, although two recent U.S. studies incorporated prenatal hospital admissions as well (Gilbert et al., 2003, Schmitt et al., 2006). One study included any subsequent transfers until the mother was ultimately discharged (Gilbert et al., 2003). Use of the estimates from the IHC cohort data used...

The primary sources of funding for research on premature birth and individuals who survived preterm birth are NIH, the Centers for Disease Control and Prevention (CDC), and nonprofit voluntary health or philanthropic organizations, such as the March of Dimes and the Burroughs-Wellcome Fund. These agencies and organizations support research related to the basic science of the events that lead to preterm labor, interventions that can be taken to prevent pre-term labor, treatments for infants who...

Because the constellation of socioenvironmental variables known to affect the risk of pre-term birth is not equitably distributed across racial-ethnic groups, the interaction of these factors with genetic predispositions may also produce highly disparate clinical outcomes. As discussed in the previous section, this area needs to be further investigated. In summary, the question of whether genetics explains a substantial proportion of health disparities in preterm birth, is largely unanswered....

Another possible reason for a genetic influence on racial-ethnic disparities in preterm birth rates is the variation in the effect of a given genetic variant between racial groups. However, data that can be used to either support or disprove this hypothesis are limited. One study examined the genetic effects of 43 validated gene-disease associations among 697 study populations of various descents (Ioannidis et al., 2004). The frequencies of the genetic marker of interest in the control...

Medicaid pays for a large share (40 percent) of the medical costs associated with preterm birth (Russell et al., 2005). Because low-income pregnant women are eligible for Medicaid, Medicaid pays for about a third of all deliveries in the United States (Rosenbaum, 2002). Most children in the United States receive health insurance through a parent's employment. The next most common sources of health insurance for children are the Medicaid program and the State Children's Health Insurance Program...

Health, as formulated by the World Health Organization (WHO, 1958) is a 'state' of complete physical, mental and social well-being and not merely the absence of disease or infirmity. Health-related quality of life (HRQL) is a narrower concept that considers the net impact or consequence of a disease or impairment and implicitly reflects the personal values of the individual (Gill and Feinstein, 1994). Measurement of HRQL can be used for comparisons with different disease conditions, as well as...

The concept of prematurity involves biological immaturity for extrauterine life. Maturation is the process of achieving full development or growth. Infants born preterm have immature organ systems that often need additional support to survive. The degree of maturity, therefore, is the major determinant of mortality and morbidity (the short- and long-term complications) of preterm birth. Accurate definitions of preterm birth are essential for comparing and interpreting the various studies that...

Because preterm birth is concentrated in populations of low socioeconomic status, the cost of preterm birth generates a considerable burden on public programs, many of which target low-income and other vulnerable populations. As noted above, pregnant women who have received ART may not be representative of all pregnant women (among other things, evidence suggests that they are from socioeconomically advantaged backgrounds). Thus, this fact should be taken into account when generalizations are...

Better define the problem of preterm birth with improved data Recommendations included in this category pertain to the need for improved collection of surveillance and descriptive data in order to better define the nature and scope of the problem of preterm birth. 2. Study the economic outcomes for infants born preterm Conduct clinical and health services research investigations Recommendations in this category pertain to the need to examine and improve the clinical treatment of women who...

Traditionally, preterm delivery was thought to result from events that occurred at about the time of labor onset. The finding of elevated CRH levels before midgestation in association with preterm delivery suggests that some events triggering preterm delivery may be set in motion earlier in pregnancy than was previously thought (Hobel et al., 1999 Leung et al., 1999 McLean and Smith, 1999 McLean et al., 1999). A growing body of evidence now suggests that complications that become apparent...

Although the complex interplay between the duration of pregnancy, fetal and infant size and maturity, and how they are measured are sources of some confusion, evaluation of the interrelationships among these factors provides an opportunity to gain some insight into the factors contributing to preterm birth. For example, racial disparities in all aspects of health have long been recognized, and the causes of these disparities are poorly understood. Public health databases with data on births,...

Infertility treatments have allowed thousands of couples who have difficulty conceiving to fulfill their desire to have children. In the United States in 2002, 7.3 million women, or 12 percent of women ages 15 to 44, had physical difficulty becoming pregnant or carrying a baby to term. Approximately 2.1 million of these women, or 7 percent of all women between the ages of 15 and 44, were infertile, defined as not becoming pregnant after 12 months when the couple is not using contraception (CDC,...

FIGURE 1-7 Percentage of live births from ART by maternal age, 2002. SOURCE NCCDPHP (2005). In addition to the health problems associated with preterm birth described at the outset of this chapter, preterm birth is accompanied by broad emotional and financial costs and lost opportunities for families. The birth and hospitalization of preterm infants are associated with maternal distress (Eisengart et al., 2003 Singer et al., 2003) and maternal depressive symptoms (Davis et al., 2003)....

Obstetricians are taught that their first obligation and priority is the mother's health but that women and families are willing to accept some degree of increased risk to the mother if it will benefit her fetus (see Appendix C for a discussion of ethical issues). A decision to arrest pre-term labor may increase the risk to both the mother and the fetus if the pregnancy is complicated by bleeding, hypertension, or infection. A lesser risk usually attends uncomplicated preterm labor but...

The period of gestation is one of the most important predictors of an infant's subsequent health and survival. In 2004, more than 500,000 infants, or 12.5 percent of all infants, were born preterm, which is considered birth at less than 37 completed weeks of gestation (CDC, 2005a). On the basis of new estimates provided in this report, the annual societal economic burden associated with preterm birth in the United States was in excess of 26.2 billion in 2005 (this estimate represents a lower...

Kangaroo care provides skin-to-skin care by placing the naked preterm infant in an upright position between the mother's breasts and allows unlimited breast-feeding. This concept of caring for preterm infants originated in Bogota, Columbia, as a low-cost way to assist preterm infants with temperature regulation, nutrition, and stimulation (Charpak et al., 1996). Kangaroo care is initiated after a routine period of stabilization after birth. A number of studies from developing countries,...

At all times during a pregnancy, accurate dating of the pregnancy and accurate estimates of fetal maturity provide better information for decision making by the health care provider and the family. Although this is especially true for the high-risk pregnancies noted above, the information also assists the health care provider and the family with making decisions on the how a threatened preterm delivery is managed and the optimal timing and mode of delivery as a pregnancy approaches fullterm....

Obstetricians and gynecologists are charged significantly higher premiums for liability insurance than physicians in other specialties (MacLennan et al., 2005). When clinical departments must pay 150,000 or 165,000 a year for a faculty member's malpractice insurance, as they are in Pennsylvania and Alabama, respectively, it absorbs resources that might otherwise be available to support research. The AAMC Report on Medical School Faculty Salaries, 2003-04 (AAMC, 2005) shows that the mean...

Several studies found that women who live in an area with high levels of air pollution are more likely to deliver preterm than women who live in less polluted areas. Women who live near petroleum refinery plants (Lin et al., 2001 Yang et al., 2004a), petrochemical industrial complexes (Yang et al., 2002a,b), or industrial districts with increased levels of emission of air contaminants from multiple sources (including petrochemical, petroleum, steel, and shipbuilding industries) (Tsai et al.,...

Several studies have identified young maternal age as an important risk factor for preterm birth (Amini et al., 1996 Branum and Schoendorf, 2005 Copper, 1995 Fraser et al., 1995 Hediger et al., 1997 Satin et al., 1994 Scholl et al., 1992, 1994). Hediger et al. (1997) found that young adolescents (less than 16 years of age at the time of their last menstrual period), especially those of young gynecological age (within 2 years of menarche), had a twofold greater risk for preterm delivery compared...

The inclusion of social conditions in models of cumulative risk depends on the ability to validly measure the various components of social context at appropriate scales of influence. In their simplest form, multilevel studies typically include assessments at the individual and community levels by the use of some standard administrative unit to define community (e.g., health area, zip code, census tract, or block). For example, exposure to poverty or substandard housing may be measured at the...

Infants born preterm are more likely than infants born full term to die during the neonatal period (first 28 days) and infancy (first year), and mortality rates increase proportionally with decreasing gestational age or birth weight (Alexander et al., 1999 Allen et al., 2000 Lemons et al., 2001 Martin et al., 2005) (see also Figures 9-2 and 9-3 in Chapter 9 and Appendix B). The leading causes of infant mortality in the United States are preterm birth, low birth weight, and birth defects so...

Als devised a highly organized comprehensive system for providing neurodevelopmental support in a NICU (Als, 1998). This system, commonly known as NIDCAP, has generated much interest and is often equated with NICU developmental care (Ashbaugh et al., 1999). Its systematic implementation requires development of NICU developmental care teams with dedicated staff trained and certified in NIDCAP, the systematic observation of the behavior of the infants, the coordination of care, and careful...

Among the earliest concerns about the health of premature infants was the association between preterm delivery and neurodevelopmental disabilities. Neurodevelopmental disabilities are a group of chronic interrelated disorders of central nervous system function due to malformation of or injury to the developing brain. The spectrum of neurodevelopmental disabilities includes the major disabilities cerebral palsy (CP) and mental retardation. Sensory impairments include visual impairment and...

Nonmedical interventions, such as social support, reduction of stress, improved access to prenatal care, and reduced physical activity, can be used to reduce the rates of preterm birth and were reviewed in Chapter 3. A recent study examined the rates of low birth weight among participants in a Medicaid-funded prenatal program for high-risk women (Ricketts et al., 2005). The results indicated that the infants of women who stopped smoking had a rate of low birth weight of 8.5 percent, whereas the...

The relationships between frequent or chronic pain, the stress response, cortisol levels, and the neurodevelopment of the preterm infant are extremely complex (Grunau, 2002 Clin Perinatol 29 373 Grunau et al., 2006 Seminars in Perinatology in press). The fetus or preterm infant responds to painful stimuli with increases in cortisol and endorphin levels as early as 23 weeks of gestation, but the neurotransmitters that attenuate pain develop later in postnatal life (Anand, 1998 Biol Neonate 73 1...

The emerging literature on personal resources warrants attention in multilevel research attempts to understand preterm birth better. The term personal resources refers to individual differences in views about one's self and the world, such as self-esteem, mastery, perceived control, and optimism. These are conceptualized as relatively stable characteristics of individuals that are generally protective of the individual' s health and that function as coping resources (Lachman and Weaver, 1998...

Polychlorinated biphenyls (PCBs) are industrial chemicals that were manufactured and used commercially as mixtures of congeners, with each congener distinguished by the number and pattern of chlorination of the biphenyl rings. Certain PCB congeners persist in the environment, are poorly metabolized, and biomagnify in the food chain. These characteristics result in increased opportunities for human exposure. The production and commercial use of PCBs were discontinued in most countries in the...

In the 1960s to 1970s, missing or inaccurate gestational age data for many newborns led to a search for postnatal methods of determining gestational age. These methods invariably focused on the degree of infant maturation (Allen, 2005a Philip et al., 2003). Farr et al. (1966) described the maturation of a number of external physical characteristics in preterm and term infants. Hittner et al. (1977, 1981) proposed a systematic method of grading the disappearance of the pupillary membrane (i.e.,...

The fetal membranes (amnion and chorion) abut the maternal decidua and rest upon a collagenous basement membrane of type II and IV collagen. Beneath this layer is a fibrous layer that contains collagen types I, III, V, and VI. Thus, collagen provides major structural strength for the membranes. Membrane rupture is a process similar to wound healing, a process in which collagen is degraded (Malak and Bell, 1994). MMPs are the only family of enzymes that act to degrade collagen and play a major...

The prevention of preterm birth has been attempted by the use of interventions aimed at each of the risk factors described in the previous chapters, largely without success (Table 9-5). TABLE 9-5 Summary of Studies of Medical Interventions to Prevent Preterm Birth tion Studied Interventions Tested in RCT Outcome Nutritional supplements Vitamins C and E No benefit, vitamin C-CPEP Trial, inadequate data Prior preterm birth and bacterial vagi-nosis Antibiotics during pregnancy Mixed results...

Lost labor market and household productivity for individuals born preterm may result from disabling conditions, from the more subtle effects of cognitive or behavioral deficits, or from lower intelligence quotients. Lost productivity can result from either premature mortality or heightened morbidity, in which the ability to work or the amount of work, or both, could be affected. One complication for the calculation of indirect mortality and morbidity costs that is generally ignored when infant...

Despite the many advantages and advances in knowledge attributable to genomics and mi croarray analysis, these approaches have several limitations. Although the human genome contains approximately 30,000 genes, many more messenger RNA transcripts potentially coding for different proteins exist because of the alternate splicing of genes. Depending on codon bias, there is only a limited relationship between the expression of a gene and the amount of protein expression directed by that gene. The...

Although controversy exists over inclusion criteria for racial and ethnic subgroups, racial and ethnic disparities in preterm birth rates, birth weight distributions for gestational age, neonatal and infant mortality rates, and gestational age- and birth weight-specific neonatal mortality rates have been consistently reported (see Appendix B). In the United States in 2003, preterm birth rates were 10.5 for Asian and Pacific Islanders, 11.3 percent for whites, and 17.8 percent for African...

The large disparities in the proportion of preterm births and other birth outcomes between racial and ethnic groups in the United States have been persistent and troubling. The categorization of racial and ethnic groups is difficult and controversial because there is no simple method for defining these groups or subgroups. However, it is important to collect data on race and ethnicity to document and assess health status and health outcomes for various groups of the U.S. population. The U.S....

Agencies should be committed to sustained and vigorous support for research on the etiologies ofpreterm birth to fill critical knowledge gaps. Areas to be supported should include the following The physiological and pathologic mechanisms of parturition across the entire gesta-tional period as well as the pregestational period should be studied. The role of inflammation and its regulation during implantation and parturition should be studied. Specifically, perturbations to the immunologic and...

American College of Obstetricians and Gynecologists, the American Society for Reproductive Medicine, and state and federal public health agencies should institute guidelines that will reduce the number of multiple gestations. Particular attention should be paid to the transfer of a single embryo and the restricted use of superovulation drugs and other nonassisted reproductive technologies for infertility treatments. In addition to mandatory reporting to the Centers for Disease Control and...

Women at increased risk of preterm labor. Researchers should investigate ways to improve methods to identify and treat women with an increased risk of preterm labor. The content and structure of prenatal care should include an assessment of the risk of preterm labor. Improved methods for the identification of women at increased risk of preterm labor both before pregnancy and in the first and second trimesters are needed. Combinations of known markers of preterm labor (e.g., a prior preterm...

National Institutes of Health, the U.S. Department of Education, other funding agencies, and investigators should develop guidelines for determining and reporting outcomes for infants born preterm that better reflect their health, neurodevelopmental, educational, social, and emotional outcomes across the life span and conduct research to determine methods that can be used to optimize these outcomes. Outcomes should be reported by gestational age categories, in addition to birth weight...

Recommendation V-1 The National Institutes of Health and private foundations should establish integrated multidisciplinary research centers. The objective of these centers will be to focus on understanding the causes of preterm birth and the health outcomes for women and their infants who were born preterm. Consistent with the Roadmap initiative of the National Institutes of Health, these activities should include the following Basic, translational, and clinical research involving the clinical,...

THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences...

Early attempts to improve an infant's environment focused on providing sensory stimuli, including rocking, stroking, holding, and moving, as well as auditory stimuli (e.g., the mother's recorded voice and music) and visual stimuli, either alone or in combination (Aucott et al., 2002 Barnard and Bee, 1983 Mueller, 1996). Most studies of these interventions were flawed by small sample sizes, inadequate controls, or a failure to mask outcome evaluators. Few studies addressed the difficulty of...

Many outcomes researchers recognize the limitations of reporting the outcomes for individuals born preterm only in terms of the diagnoses of specific neurodevelopmental disabilities and have defined and reported on the severity of disability as well. For 8-year-olds born in 1991 and 1992 in Australia, severe disability (i.e., severe CP, blindness, or IQ scores 3 or more standard deviations below the mean) occurred in 9 percent of the children with birth weights of less than 1,000 grams and 12...

Much of the literature on the rates of receipt of special education by newborn status has focused on LBW infants, particularly VLBW and extremely-low-birth-weight infants, and has not been estimated from population-based samples (Pinto-Martin et al., 2004). In a 9-year follow-up of a cohort of 1,105 infants born between September 1984 and June 1987 in central New Jersey, both VLBW and birth at a gestational age of less than 28 weeks were found to be significantly associated with the receipt of...

Stress is increasingly being recognized as an important risk factor for preterm delivery. Stress may be simply defined as any challenge psychological or physical that threatens or that is perceived to threaten homeostasis (i.e., the stability of the internal milieu of the organism). The epidemiological evidence linking maternal psychological stress to prematurity is reviewed in Chapter 3. Several pathways linking maternal psychological stress and prematurity have been proposed, including...

A number of maternal sociodemographic characteristics are associated with higher rates of preterm delivery. Specifically, maternal age (less than_16 years of age or 35 years of age or older), marital status (unmarried or cohabiting), race or ethnicity (African American or American Indian), and socioeconomic condition (low income or educational attainment) have been identified as risk factors for prematurity. Most of these sociodemographic factors are closely intertwined with behavioral risk...

Preterm birth has many potential pathways (Figure 6-2). In the past, obstetricians and epidemiologists have had a tendency to combine, for statistical purposes, all preterm births occurring between 22 and 37 weeks of gestation. This has obscured the opportunity to study pre-term birth as a final common end point and has led to uniform, largely empirical, and unsuccessful treatment strategies. It is now clear that the causes of preterm labor and multifactorial and vary according to gestational...

Income supports for low-income families are also provided through the TANF program, which replaced the Aid to Families with Dependent Children (AFDC) program in 1997. In 1996, the U.S. Congress passed the Personal Responsibility Work Opportunity and Reconciliation Act (PRWORA), known as welfare reform, which ended the long-standing federal entitlement to cash assistance for the poor (AFDC). Federal mandates imposed a 5-year lifetime cap on benefits for individuals, required recipients to work...

The Title V Maternal and Child Health programs provide a variety of services for children with chronic health conditions. Approximately 85 percent of the federal funds from Title V Maternal and Child Health programs go directly to the states, which are given wide flexibility in their use for maternal and child health programs. About one-third of the state allocations go to programs for children with special health care needs about 50 percent of the funds are used for preventive programs in...

A major roadblock to advancing research on preterm birth and its consequences is the lack of experienced clinician scientists to conduct research and serve as mentors in obstetrics and gynecology departments as well as in pediatrics departments. Experienced mentors are needed to help research trainees plan their careers and support their development. Particularly needed are investigators who are successful with receiving funding from the federal research funding system. However, it is not clear...

As many reports have indicated, the proportion of preterm births has risen fairly steadily since 1990 (Figure 1-1). Note, however, that some of the change in the rate of preterm birth is likely reflective of changes in the way in which gestational age is measured (see Chapter 2 for a discussion). In the early to mid-1990s the percentage of preterm births remained stable at about 11 percent. There was a slight decline from 11.8 percent in 1999 to 11.6 percent in 2000. In 2004, the percentage...

The complications of the newborn period noted in this chapter reflect in part the difficulty of establishing extrauterine life with immature organs. However, some of these complications may also reflect the interventions used in the NICU to sustain life. The question about variations in complication rates as a function of differences in management practices in the NICU was initially raised by a report of the substantial variations in the rate of bronchopumonary dysplasia or chronic lung disease...

Two issues that deserve focus because of the applicability of 45 CFR 46, Subpart B, are research at the threshold of viability and the ability of adolescent pregnant women to consent to research. In the 2001 revision to Subpart B, the term neonate was used as applied to research involving pregnant women, human fetuses, neonates of uncertain viability, or nonviable neonates. Subpart B defines a viable neonate as one that, given the benefit of medical therapy, is able to survive after delivery to...

A relatively small number of studies have assessed the effects of daily stressors on preterm birth but have shown disappointing results (Paarlberg et al., 1996 Wadhwa et al., 1993). It is possible that these measures do not capture levels of stress exposure high enough to influence pathways to prematurity. Although daily stressors may operate in combination with other stress exposures, such as major life events, and interact with responses such as anxiety or depression to contribute to the risk...

Among the behavioral and psychosocial factors considered, the one that shows the most consistent evidence of having an adverse impact on the risk of preterm birth is cocaine use. Dietary constituents have been examined to a limited degree, with mixed evidence on the potential benefits of increased levels of iron, long-chain fatty acids, folate, and vitamin C being found. Although none of these dietary constituents is well established as having effects that prevent pre-term birth, all warrant...

Several studies specifically analyzed whether a stage of gestation for exposure to air pollutants is the most strongly associated with preterm birth. The results have been inconsistent, with some studies reporting significant associations early or late in gestation. Exposure to sulfur dioxide (Bobak, 2000 Mohorovic, 2004), total suspended particulates (Bobak, 2000), and nitrogen dioxide (Maroziene and Grazuleviciene, 2002) in the first trimester, but not the second or the third trimester, of...

Except for women who have used assisted reproductive technologies (ARTs e.g., in vitro fertilization), the timing of the initiation of a pregnancy is imputed from the first day of the mother's last menstrual period (LMP). Obstetricians have traditionally confirmed pregnancy dating by combining information regarding the mother's LMP, periodic measurements of the mother's abdomen and when fetal heart sounds and movement (i.e., quickening) are detected (Rawlings and Moore, 1970). If a mother's...

Neuromaturation is a dynamic process in which the central nervous system (CNS) is formed by a continuous interaction between the programmed genetic processes encoded within the genome and then the intrauterine environment, followed by the extrauterine environment. The successive turning on and then turning off of specific genes propel development forward, whereas surrounding cells, temperature, nutrients, and unknown environmental factors influence cell division, differentiation, function,...

Several longitudinal studies have attempted to ascertain the effects of early intervention on the emotional, physical, and developmental outcomes in children born preterm or with disabilities. The Infant Health and Development Program (IHDP) is a multicentered, randomized, controlled, U.S. nationwide study of preterm infants born in 1985 at gestational ages of less than 37 weeks and with birth weights of less than 2,500 grams and their families. Infants and their families were randomly assigned...

Cerebral Palsy (CP) is a general term to describe a group of chronic conditions that impair control of movement and posture. CP is due to malformation of or damage to motor areas in the brain which disrupt the brain's ability to control movement and posture. Symptoms of CP may range from mild to severe, change over time and differ from person to person, and include difficulty with balance, walking, and fine motor tasks (such as writing or using scissors) and involuntary movements. Many people...